Fig. 3.

Conformational diversity of gp120. Protein motions can be classified into categories of hinge, shear, and refold (Left) (35). These archetypes show distinctive signatures when analyzed by enumerating secondary structure changes (horizontal axis) and by difference–distance maximum (vertical axis). Hinge motions generate large difference distances, although only a few residues refold (e.g., calmodulin, hemolysin, and transglutaminase). Shear motions show small changes with both metrics (e.g., citrate synthase and calpain). Refold motions, by contrast, show large changes with both metrics. Refolding is perhaps best epitomized by the transmembrane components of type 1 fusion machines (e.g., “F1” of parainfluenza virus, “HA2” of influenza A virus, and “gp2” of Ebola virus). This analysis shows how gp120 fits into the refold category when moving from unliganded state or between different states induced by receptor and/or antibody. In this it differs from the N-terminal components of other type 1 fusion proteins (e.g., “HA1” of influenza virus). When fixed by CD4 binding, however, these metrics indicate that primarily a single state is induced. [Like gp120, the ubiquitin-conformational ensemble (29) also forms a cluster, although one of much smaller magnitude than that of gp120; to clarify presentation, only a single point for a relatively divergent pair of ubiquitin conformations is displayed, with the ubiquitin cluster extending from this point to the origin.] Labels are italicized representations of structures for which the sequence identity is less than 40% between the two conformations.